1. FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors
- Author
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Britta Siegmund, Friederike Christen, Michael Hummel, Florentine Lewens, Almut Kunze, Jörg Sänger, Helma Freitag, Franziska Briest, Erika Berg, Ruza Arsenic, Irina Grass, Daniel Kaemmerer, Patricia Grabowski, Annelore Altendorf-Hofmann, and Thomas Knösel
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Apoptosis ,Neuroendocrine tumors ,Biology ,Young Adult ,cancer signaling ,Stomach Neoplasms ,Cell Line, Tumor ,Intestinal Neoplasms ,medicine ,Humans ,Molecular Targeted Therapy ,Mitosis ,Transcription factor ,siomycin A ,Aged ,Cell Proliferation ,Aged, 80 and over ,Chemotherapy ,Forkhead Box Protein M1 ,FOXM1 ,Cell Differentiation ,Forkhead Transcription Factors ,differentiation ,Middle Aged ,gastroenteropancreatic neuroendocrine neoplasms ,medicine.disease ,In vitro ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,Oncology ,Cell culture ,Cancer research ,Peptides ,Research Paper - Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors that need to be molecularly defined to obtain novel therapeutic options. Forkheadbox protein M1 (FOXM1) is a crucial transcription factor in neoplastic cells and has been associated with differentiation and proliferation. We found that FOXM1 is strongly associated with tumor differentiation and occurrence of metastases in gastrointestinal NENs. In vitro inhibition by the FOXM1 inhibitor siomycin A led to down-regulation of mitotic proteins and resulted in a strong inhibitory effect. Siomycin A decreased mitosis rate, induced apoptosis in GEP-NEN cell lines and exerts synergistic effects with chemotherapy. FOXM1 is associated with clinical outcome and FOXM1 inhibition impairs survival in vitro. We therefore propose FOXM1 as novel therapeutic target in GEP-NENs.
- Published
- 2015
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